Synapsins as regulators of neurotransmitter release
Synapsins as regulators of neurotransmitter release
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DOI：
10.1098/rstb.1999.0378
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发表时间：
1999-02-28
期刊：
影响因子：
--
通讯作者：
Greengard, P
中科院分区：
文献类型：
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作者：
Hilfiker, S;Pieribone, VA;Greengard, P
理解神经元传递的关键问题之一是确定大量蛋白质的作用(S)，这些蛋白质定位于突触前终末，被认为参与突触小泡生命周期的调节。突触素是神经元特异性磷酸蛋白的多基因家族，是突触小泡上含量最丰富的蛋白质。突触素在体外能够与突触小泡的脂质和蛋白质成分以及包括肌动蛋白在内的各种细胞骨架蛋白相互作用。这些和其他研究已经导致了一种模型，在该模型中，突触蛋白通过将突触小泡相互捆绑在一起，并形成基于肌动蛋白的细胞骨架网络，在活动区附近维持一个储备池的小囊泡。突触素功能在各种准备中的扰动导致这个储备池的选择性破坏和突触抑制的增加，这表明突触蛋白依赖的囊泡簇需要维持神经递质的释放，以响应高水平的神经元活动。在最近对鱿鱼巨型突触进行的一项研究中，突触素功能的扰动导致了小泡储备池的选择性破坏，此外，还导致了神经递质释放动力学的抑制和减慢，表明突触蛋白在小泡对接下游发挥了第二种作用。这些数据表明，突触素参与了两种截然不同的反应，这两种反应对突触前神经末梢的胞吐作用至关重要。这篇综述描述了我们目前对突触蛋白调节突触传递的分子机制的了解，而突触蛋白在突触形成和稳定中的作用越来越多地被证明是超出了本综述的范围。
One of the crucial issues in understanding neuronal transmission is to define the role(s) of the numerous proteins that are localized within presynaptic terminals and are thought to participate in the regulation of the synaptic vesicle life cycle. Synapsins are a-multigene family of neuron-specific phosphoproteins and are the most abundant proteins on synaptic vesicles. Synapsins are able to interact in vitro with lipid and protein components of synaptic vesicles and with various cytoskeletal proteins, including actin. These and other studies have led to a model in which synapsins, by tethering synaptic vesicles to each other and to an actin-based cytoskeletal meshwork, maintain a reserve pool of vesicles in the vicinity of the active zone. Perturbation of synapsin function in a variety of preparations led to a selective disruption of this reserve pool and to an increase in synaptic depression, suggesting that the synapsin-dependent cluster of vesicles is required to sustain release of neurotransmitter in response to high levels of neuronal activity. In a recent study performed at the squid giant synapse, perturbation of synapsin function resulted in a selective disruption of the reserve pool of vesicles and in addition, led to an inhibition and slowing of the kinetics of neurotransmitter release, indicating a second role for synapsins downstream from vesicle docking. These data suggest that synapsins are involved in two distinct: reactions which are crucial for exocytosis in presynaptic nerve terminals. This review describes our current understanding of the molecular mechanisms by which synapsins modulate synaptic transmission, while the increasingly well-documented role of the synapsins in synapse formation and stabilization lies beyond the scope of this review.